• IMMUNE NETWORK
• /
• v.9 no.4
• /
• pp.127-132
• /
• 2009

Background: Toll-like receptors (TLRs) play a fundamental role in innate immunity through their capacity to recognize pathogen-associated molecular patterns. Also, TLRs that are expressed in T cells are reported to function as co-stimulatory receptors. However, the functional capacity of TLRs on CD4 T and CD8 T cells has not been directly compared. Here we compared CD4 and CD8 T cell responses to TLR2 ligand plus TCR-mediated stimulation. Methods: TLR2 expression was analyzed on T cell subsets under naive and alloantigen-primed conditions. We analyzed the effects of TLR2 co-stimulation on proliferation and survival of T cell subsets in vitro when stimulated with soluble anti-CD3 in the presence or absence of synthetic ligand $Pam_3CSK_4$. Results: TLR2 expression on CD8 T cells was induced following activation; this expression was much higher than on CD4 T cells. Thus, the molecule was constitutively expressed on Listeriaspecific memory CD8 T cells. Based on these expression levels, proliferation and survival were markedly elevated in CD8 T cells in response to the TLR2 co-stimulation by $Pam_3CSK_4$ compared with those in CD4 T cells. Conclusion: Our data show that TLR2 co-stimulation is more responsible for proliferation and survival of CD8 T cells than for that of CD4 T cells.

• IMMUNE NETWORK
• /
• v.11 no.6
• /
• pp.336-341
• /
• 2011

T cell receptor (TCR) signaling plays a critical role in T cell development, survival and differentiation. In the thymus, quantitative and/or qualitative differences in TCR signaling determine the fate of developing thymocytes and lead to positive and negative selection. Recently, it has been suggested that self-reactive T cells, escape from negative selection, should be suppressed in the periphery by regulatory T cells (Tregs) expressing Foxp3 transcription factor. Foxp3 is a master factor that is critical for not only development and survival but also suppressive activity of Treg. However, signals that determine Treg fate are not completely understood. The availability of mutant mice which harbor mutations in TCR signaling mediators will certainly allow to delineate signaling events that control intrathymic (natural) Treg (nTreg) development. Thus, we summarize the recent progress on the role of TCR signaling cascade components in nTreg development from the studies with murine model.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.7
• /
• pp.4325-4328
• /
• 2013

Introduction: The influence of season at diagnosis on cancer survival has been an intriguing issue for many years. Most studies have shown a possible correlation in between the seasonality and some cancer type survival. With short expected survival, lung cancer is an arena that still is in need of new prognostic factors and models. We aimed to investigate the effect of season of diagnosis on 3 months, 1 and 2 years survival rates and overall survival of non small cell lung cancer patients. Materials and Methods: The files of non small cell lung cancer patients that were stages IIIB and IV at diagnosis were reviewed retrospectively. According to diagnosis date, the patients were grouped into 4 season groups, autumn, winter, spring and summer. Results: A total of 279 advanced non small cell lung cancer patients' files were reviewed. Median overall survival was 15 months in the entire population. Overall 3 months, 1 and 2 years survival rates were 91.0%, 58.2% and 31.2% respectively. The season of diagnosis was significantly correlated with 3 months survival rates, being diagnosed in spring being associated with better survival. Also the season was significantly correlated with T stage of the disease. For 1 and 2 years survival rates and overall survival, the season of diagnosis was not significantly correlated. There was no correlation detected between season and overall survivals according to histological subtypes of non small cell lung cancer. Conclusion: As a new finding in advanced non small cell lung cancer patients, it can be concluded that being diagnosed in spring can be a favorable prognostic factor for short term survival.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• v.37 no.1
• /
• pp.15-20
• /
• 2011

Introduction: The characteristics of oral tongue squamous cell carcinomas (SCC) and the treatment results were reviewed to determine the appropriate treatment strategies. Materials and Methods: The medical records of 140 patients diagnosed and treated for oral tongue SCC at Yonsei University Health System from January 1995 to December 2004 were reviewed. For statistic analysis, the survival rate was determined using the Kaplan-Meier method with SPSS version 12.0, and the difference in survival rates was evaluated using a log-rank test. Results: The mean age of the patients with oral tongue SCC patients was 55 (19-85 years old). According to the T, N and pathologic stage, the patients were distributed from a higher to a lower incidence of cases, as follows: T2 (46.4%), T1 (37.9%), T4 (8.5%), and T3 (7.1%); N0 (65%), N1 (20.7%), N2 (13.6%), and N3 (0.7%); and stage I (31.4%), stage II(25.7%), stage IV (22.2%), and stage III (20.7%). Local and regional recurrence and distant metastasis was present in 13.6%, 5% and 4.2% of patients, respectively. The five-year survival rate was 72.2%, and the prognostic factors for oral tongue SCC included neck metastasis, pathologic stage of the disease, cell differentiation, treatment modality, neck dissection as part of the treatment plan, and neck node recurrence. Discussion: It is suggested that ipsilateral neck dissection or bilateral neck dissection should be selected as a treatment of tongue SCC patients with advanced stage.

• Radiation Oncology Journal
• /
• v.13 no.1
• /
• pp.19-26
• /
• 1995

Purpose : Surgery is the treatment of choice for resectable non-small cell lung cancer. For patients who are medically unable to tolerate a surgical resection or who refuse surgery, radiation therapy is an acceptable alternative. A retrospective analysis of Patients with stage I non-samll cell lung cancer treated with curative radiation therapy was performed to determine the results of curative radiation therapy and patterns of failure, and to identify factors that may influence survival. Materials and Methods : From 1986 through 1993, 39 Patients with T2N0M0 non-small cell lung cancer were treated with curative radiation therapy at department of radiation oncology, Kyungpook national university hospital. All Patients were not candidates for surgical resection because of either Patient refusal (16 patients), poor pulmonary function (12 patients), old age (7 patients), Poor Performance (2 patients) or coexisting medical disease (2 patients). Median age of patients was 67 years. Histologic cell type was squamous cell carcinoma in 36, adenocarcinoma in 1, large cell carcinoma in 1 and mucoepidermoid carcinoma in 1. All patients were treated with megavoltage irradiation and radiation dose ranged from 5000cgy to 6150cGy with a median dose of 6000cGy. The median follow-up was 17 months with a range of 4 to 82 months, Survival was measured from the date therapy initiated. Results : The overall survival rate for entire Patients was $40.6\%$ at 2 years and $27.7\%$ at 3 years, with a median survival time of 21 months. The disease-free survival at 2 and 3 years was $51.7\%$ and $25.8\%$, respectively. Of evaluable 20 patients with complete response, 15 patients were considered to have failed. Of these, 13 patients showed local failure and 2 patients failed distantly. Response to treatment (p=0.0001), tumor size (p=0.0019) and age (p=0.0247) were favorably associated with overall survival. Only age was predictive for disease-free survival (p = 0.0452). Conclusion : Radiation therapy is an effective treatment for small (less than 3cm) tumors, and should be offered as an alternative to surgery in elderly or infirm patients. Since local failure is the prominent Patterns of relapse, potential methods to improve local control with radiation therapy are discussed.

• Clinical and Experimental Otorhinolaryngology
• /
• v.11 no.4
• /
• pp.259-266
• /
• 2018

Objectives. Carcinomas of the external auditory canal (EAC) are rare, and management remains challenging. Previous studies seeking prognostic factors for EAC cancers included cancers other than carcinomas. In this study, we analyzed the treatment outcomes of, prognostic factors for, and survival rates associated with specifically squamous cell carcinoma (SCC) of the EAC. Methods. A retrospective review of 26 consecutive patients diagnosed with SCCs of the EAC in a 10-year period was performed in terms of clinical presentation, stage, choice of surgical procedure, and adjunct therapy. Overall survival (OS) and recurrence-free survival (RFS) were calculated and univariate analysis of prognostic factors was performed. Results. The median age of the 26 patients with SCCs of the EAC was 63 years (range, 40 to 72 years), and 16 males and 10 females were included. According to the modified University of Pittsburgh staging system, the T stages were T1 in 11, T2 in six, T3 in four, and T4 in five cases. The surgical procedures employed were wide excision in three cases, lateral temporal bone resection (LTBR) in 17, and extended LTBR in four, and subtotal temporal bone resection in two. Two patients underwent neoadjuvant chemotherapy, and two underwent adjuvant chemotherapy. One patient received preoperative radiation therapy, and eleven received postoperative radiation therapy. Of the possibly prognostic factors examined, advanced preoperative T stage and advanced overall stage were significant predictors of RFS, but not of OS. Conclusion. The advanced T stage and overall stage were associated with decreased survival after surgical treatment in patients with SCC of the EAC, highlighting the importance of clinical vigilance and early detection.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.12
• /
• pp.7645-7649
• /
• 2013

Background: Immune functions and their relation to prognosis in breast cancer patients have become areas of great interest in recent years. Correlations between survival outcomes and peripheral blood flow cytometry parameters are therefore of interest. Here we focused on patients with non-metastatic breast cancer (BC). Materials and Methods: A total of 29 patients with pathological confirmed breast carcinoma and flow cytometry data were assessed for overall survival (OS) and progression free survival (PFS). Results: The median age of the patients was 54 years (range, 29-83). Multivariate analysis revealed that OS was significantly associated with absolute cytotoxic T cell count (95%CI, coef 2.26, p=0.035), tumor size (95%CI, coef -14.5, p 0.004), chemotherapy (95%CI, coef 12.9, p 0.0001), MFI of CD4 (95%CI, coef -5.1, P 0.04), MFI of HLA DR (95%CI, coef -5.9, p 0.008) and tumor grade (95%CI, coef -13, P 0.049) with R-Sq(adj)=67%. Similar findings were obtained for PFS. Conclusions: OS and PFS were significantly associated with tumor grade, tumor size, chemotherapy, MFI of CD4, HLA DR and absolute cytotoxic T cell count. The study revealed that MFI of basic CD markers and absolute cytotoxic T cell number may be a prognostic factors in women with non-metastatic BC.

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.1
• /
• pp.73-78
• /
• 2014

Cell death and survival are tightly controlled through the highly coordinated activation/inhibition of diverse signal transduction pathways to insure normal development and physiology. Imbalance between cell death and survival often leads to autoimmune diseases and cancer. Death receptors sense extracellular signals to induce caspase-mediated apoptosis. Acting upstream of CED-3 family proteases, such as caspase-3, Bcl-2 prevents apoptosis. Using short hairpin RNAs (shRNAs), we suppressed Bcl-2 expression in Jurkat T cells, and this increased TCR-triggered AICD and enhanced TNFR gene expression. Also, knockdown of Bcl-2 in Jurkat T cells suppressed the gene expression of FLIP, TNF receptor-associated factors 3 (TRAF3) and TRAF4. Furthermore, suppressed Bcl-2 expression increased caspase-3 and diminished nuclear factor kappa B (NF-${\kappa}B$) translocation.

• Korean Journal of Environmental Biology
• /
• v.35 no.2
• /
• pp.152-159
• /
• 2017

For the effective seedling production of the hard shelled mussel, Mytilus coruscus, this study assessed the effects of the dietary value of live food, density, water temperature and salinity on growth and survival rate of the larvae. The optimal survival rate and growth rate were examined under differing conditions of water temperature, salinity, and rearing density for 30 days. The three groups were provided different feeding organisms, such as Isochrysis galbana and Teleaulax suecica. The mixtures were provided at a rate of $5{\times}10^4cell\;mL^{-1}$. The best growth was observed in the group with conditions $21^{\circ}C$ water temperature ($16.2{\pm}9.1{\mu}m$), 33 psu of salinity ($16.82{\pm}3.9{\mu}m$), $2500individual\;m^{-2}$ ($17.2{\pm}5.9{\mu}m$), and fed with $5{\times}10^4cell\;mL^{-1}$ of I. galbana and T. suecica mixture ($16.0{\pm}7.3{\mu}m$). The highest survival rate was found in the group at conditions $18^{\circ}C$ water temperature (66.4%), 33 psu of salinity (24.4%), $2500individual\;m^{-2}$ (65.8%), and fed with $5{\times}10^4cell\;mL^{-1}$ of I. galbana and T. suecica mixture (58.8%). We therefore conclude that the suitable culture conditions for the stable production of hard shelled mussel artificial seedlings was at 18 to $21^{\circ}C$ of temperature, 30 to 33 psu of salinity, 2500 to $5000individual\;m^{-2}$ of rearing density, and feeding supplement of $5{\times}10^4cell\;mL^{-1}$ of I. galbana and T. suecica mixture under semi running water system.

• Journal of Microbiology and Biotechnology
• /
• v.22 no.8
• /
• pp.1066-1076
• /
• 2012

Previous observations demonstrated that various immunosuppressive agents and their combination therapies can increase allograft survival rates. However, these treatments may have serious side effects and cannot substantially improve or prolong graft survival in acute graft-versus-host disease (GVHD). To improve the therapeutic potency of divalent immunoadhesins, we have constructed and produced several tetravalent forms of immunoadhesins comprising each of cytotoxic T-lymphocyte-associated antigen-4 (CTLA4), CD2, and lymphocyte activation gene-3 (LAG3). Flow cytometric and T cell proliferation analyses displayed that tetravalent immunoadhesins have a higher binding affinity and more potent efficacy than divalent immunoadhesins. Although all tetravalent immunoadhesins possess better efficacies, tetravalent forms of CTLA4-Ig and LAG3-Ig revealed higher inhibitory effects on T cell proliferation than tetravalent forms of TNFR2-Ig and CD2-Ig. In vitro mixed lymphocytes reaction (MLR) showed that combined treatment with tetravalent CTLA4-Ig and tetravalent LAG3-Ig was highly effective for inhibiting T cell proliferation in both human and murine allogeneic stimulation. In addition, both single tetravalent-form and combination treatments can prevent the lethality of murine acute GVHD. The results of this study demonstrated that co-blockade of the major histocompatibility complex class (MHC)II:T cell receptor (TCR) and CD28:B7 pathways by using tetravalent human LAG3-Ig and CTLA4-Ig synergistically prevented murine acute GVHD.